Endocrine Abstracts

Osteoporosis is defined as low bone mineral density and/or poor bone microarchitecture associated with increased risk of fractures. This chronic disease mainly affects postmenopausal women, but also older men, being increasingly considered as an age-related morbidity. Chronic glucocorticoid therapy and diabetes mellitus are also concomittant causes of osteopenia in aging subjects. The fact that osteoporosis-related fractures accompany the increased life span imposes a major challenge to our health systems. Skeletal alterations in osteoporosis are a consequence of an altered bone remodelling related to a decreased bone formation to bone resorption balance. Anticatabolic agents commonly used as osteoporosis therapies (namely, bisphosphonates) usually decrease bone formation due to their bone-remodelling inhibitory action. The first proven bone anabolic is parathyroid hormone (PTH) when administered intermittently, and as such is currently available for osteoporosis treatment. Its potential use to promote fracture healing and in tissue engineering applications is also being evaluated. PTH-related protein (PTHrP) is considered as a local PTH counterpart in bone. PTHrP within Its N-terminal region shows homology to PTH, justifying its interaction with the common PTH/PTHrP type 1 receptor (PPR) in osteoblasts, thereby modulating bone formation and bone turnover. Intermittent administration of N-terminal PTHrP peptides increases bone accrual to a similar extent to PTH in osteoporotic rodent models and in postmenopausal women. In contrast to PTH, however, bone anabolism of N-terminal PTHrP seems to occur without concomitant activation of bone resorption (thus avoiding the risk of hypercalcaemia). This interesting feature might be due to different interaction kinetics for PTH and PTHrP with the PPR. Furthermore, the PTH-unrelated C-terminal PTHrP domain exerts osteogenic actions, apparently associated with its anti-resorptive and anabolic properties, both in vitro and in vivo. Various promising options regarding the use of PTHrP-derived peptides to enhance bone accrual and bone repair will be discussed.

Declaration of funding

This study was supported by grants from Spanish Instituto de Salud Carlos III (PI050117, RD06/0013/1002, PI11/00449), Ministerio de Educación y Ciencia (SAF2005-05254), Comunidad Autónoma de Madrid (CAM; S2009/MAT-1472) and Fundación de Investigación Médica Mutua Madrileña.